Doheny Retina Institute, Doheny Eye Institute, 1450 San Pablo St., Los Angeles, CA, 90033, USA.
Graefes Arch Clin Exp Ophthalmol. 2010 Apr;248(4):457-66. doi: 10.1007/s00417-009-1153-z. Epub 2009 Jul 31.
To compare effects of multiple injections of small divided doses of intravitreal bevacizumab vs a single injection using a retinal neovascular model in rabbits.
We assigned 12 pigmented rabbits to four groups of three each. All groups received an intravitreal injection of vascular endothelial growth factor (VEGF, 10 microg) on the first day. Group A received an intravitreal loading dose of bevacizumab (0.5 mg) on day 3, followed by five smaller injections (0.15 mg), one every third day. Those in groups B and C received a single intravitreal injection of bevacizumab (1.25 mg) on day 3, followed by five injections of sham, one every third day in group C. Group D received only intravitreal VEGF. Follow-up examinations were performed for 26 days.
In groups A and B, vascular changes associated with VEGF injection decreased substantially in the first 3 days, and continued to show gradual regression during each follow-up interval. No statistically significant differences were found between the changes of mean retinal thicknesses in groups A and B in both areas. In group C, the extra sham injections did not lead to any further vascular changes. The mean retinal thickness in groups B and C did not have a statistically significant difference during the follow-up period. In group D, vascular changes resolved more gradually than in other groups. The difference in retinal thickness between group D and the other groups was statistically significant on day 6 in both groups (medullary and inferior part; p = 0.0003) and in medullary wing on day 12 (p = 0.03).
Frequent smaller doses of bevacizumab can control VEGF-induced vascular changes as well as the currently utilized model of single large monthly injections. Dividing of currently used single injection (1.25 mg) of bevacizumab to multiple small doses can control VEGF-induced vascular changes as effectively as one large injection.
比较多次小剂量玻璃体内注射贝伐单抗与单次注射治疗兔视网膜新生血管模型的效果。
将 12 只色素兔随机分为 4 组，每组 3 只。所有组均于第 1 天玻璃体内注射血管内皮生长因子（VEGF，10μg）。A 组于第 3 天给予玻璃体内负荷剂量贝伐单抗（0.5mg），随后每 3 天给予 5 次小剂量（0.15mg）注射。B 组和 C 组于第 3 天给予单次玻璃体内贝伐单抗（1.25mg）注射，随后每 3 天给予 5 次假注射，C 组给予。D 组仅给予玻璃体内 VEGF。随访 26 天。
A 组和 B 组 VEGF 注射后第 3 天血管变化明显减少，每次随访间隔均持续逐渐消退。两组视网膜平均厚度变化无统计学差异。C 组额外的假注射并未导致任何进一步的血管变化。B 组和 C 组在随访期间视网膜平均厚度无统计学差异。D 组血管变化比其他组更缓慢。第 6 天（髓质和下部分；p=0.0003）及第 12 天（髓质翼部；p=0.03），D 组与其他组之间的视网膜厚度差异有统计学意义。
频繁给予较小剂量贝伐单抗可控制 VEGF 诱导的血管变化，与目前使用的单月大剂量注射模型相当。将目前使用的单次 1.25mg 贝伐单抗注射剂量分为多次小剂量可以有效地控制 VEGF 诱导的血管变化。
